The investigators in this project will develop diverse and novel applications of transition metal-organometallics to the synthesis of combinatorial libraries. Subproject I focuses on the design of a recyclable, chiralpalladium(0)-based linker scaffold. Organic substrates will be attached to solid supports via two carbon-palladium bonds, generating selectively either enantiomer of a palladium-bonded stereogenic carbon from a single enantiomer of the linker. Subsequent insertion of unsaturated building blocks will afford organic products in a high enantiomeric purity, and allow for the recovery and recycle of the supported palladium(0) complex. This stereodivergent methodology will be validated by the synthesis of combinatorial libraries featuring nonracemic 1,2-dihydroquinolines, 2H-1-benzopyrans and pyrrolo[1,2-a]quinolines. Subproject II proposes to develop solid-supported palladium(II) and platinum(II) catalysts for electrophilic activation and subsequent functional elaboration of aromatic C-H bonds. Furthermore, the long-standing problem of adapting electrophilic aromatic substitutions to solid-phase synthesis will be addressed by screening and modification of the existing acid-stable resins and linkers. The new solid-phase methodology will be used to establish a synthetically powerful sequence of palladium(II)-palladium(0) catalyzed reactions for the generation of diverse arylated libraries. Subproject III aims to develop a novel, highly practical and general iodocyclization protocol for the generation of an array of 1-iodo-2-aryl-substituted heterocycles. Building blocks with this motif will be further diversified by three alternative palladium-catalyzed cross-coupling and or annulation processes that generate multiple new carbon-carbon bonds. The two-step sequence of iodocyclization/palladium-catalyzed annulation will be applied to both solution and solid-phase synthesis of combinatorial libraries of diverse heterocycles.